Symptomatic primary biliary cirrhosis (PBC) appears to be a uniformly fatal disease characterized by slowly progressive intrahepatic cholestasis due to a chronic non-suppurative destructive cholangitis involving the septal and larger interlobular bile ducts. Trials of corticosteroids and azathioprine have not shown that these agents effectively inhibit the progression of the disease or increase survival. Because certain chronic inflammatory diseases appear to respond favorably to alkylating agents but not to azathioprine, a controlled randomized trial of an alkylating agent for the treatment of PBC has been initiated. The alkylating agent chosen for the trail was chlorambucil. Twenty-four patients (23 women, 1 man; ages 34-63) have been admitted this trial: 13 were randomized to the treatment and 11 to the control group. Twelve patients have been followed for 2 years. Among these 12 (7 treated, 5 controls) 3 of the untreated patients hve developed bleeding from esophageal varices and 2 have had significant deepening of jaundice (bilirubin rising J 10 mg% since admission into the trial). None of the treated patients have developed variceal belleding or deepening of jaundice.